Acute Pancreatitis as a First Presentation of Granulomatosis With Polyangiitis

ABSTRACT Granulomatosis with polyangiitis (GPA) is a rare necrotizing antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation in small-sized arteries. Gastrointestinal involvement is exceedingly rare in GPA. Here, we present a case of recurrent acute pancreatitis as the initial presentation of GPA. The diagnosis was made based on radiological and pathological findings of acute pancreatitis in conjunction with positive anti-PR3 antibody which is strongly associated with GPA. Systemic vasculitides are rare but important to consider in cases of idiopathic acute pancreatitis. Early diagnosis and therapy allow for high rates of remission and improved survival rates.


INTRODUCTION
Granulomatosis with polyangiitis (GPA) is a rare necrotizing antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation in small-sized arteries. GPA often presents with nonspecific constitutional symptoms and commonly involves a triad of (i) symptoms from the upper (nasal obstruction, sinusitis, and crusting rhinitis) and lower respiratory tract (lung nodules and alveolar hemorrhage), (ii) systemic vasculitis, and (iii) kidney involvement (necrotizing glomerulonephritis). 1,2 However, gastrointestinal involvement is exceedingly rare and only occurs in about 5%-11% of GPA cases. 3 Specifically, recurrent acute pancreatitis is even more uncommon.

CASE REPORT
A 48-year-old woman was seen in an outpatient gastroenterology clinic for recurrent idiopathic pancreatitis. She reported a 6-month history of intermittent sharp epigastric pain radiating to the back not associated with meals. This abdominal pain was associated with a rise in lipase. These symptoms were not associated with diarrhea or other changes in bowel habits. The patient noted having episodes of acute sinusitis shortly before the onset of her epigastric pain. Her initial laboratory work revealed normal creatinine 79, normal liver enzymes, elevated total bilirubin 24, lipase 316, mildly high C-reactive protein 16.1, and erythrocyte sedimentation rate 27 which normalized on repeat blood work. Abdominal ultrasound was unremarkable with no gallstones and intrahepatic or extrahepatic duct dilatation. An abdominal magnetic resonance imaging (MRI) revealed segmental enlargement of the distal tail/ body of the pancreas consistent with resolving focal pancreatitis ( Figure 1). A repeat abdominal MRI 5 weeks later revealed progression of pancreatic swelling and signal abnormality with intermittent narrowing of the pancreatic duct ( Figure 1). These findings were suspicious for an inflammatory pancreatic process such as autoimmune pancreatitis. The patient then underwent an endoscopic ultrasound-guided examination and fine-needle aspirate of her pancreas. Of note, the papilla appeared normal endoscopically. Pathology revealed focal chronic pancreatitis with fibrosis and mild lymphocytic infiltrate, which was not consistent with autoimmune pancreatitis (Figure 2). She was then treated empirically with a 3-month course of prednisone 40 mg daily with a taper and had significant improvement in her symptoms as well as interval resolution of pancreatic inflammation on repeat MRI ( Figure 1). After discontinuation of her steroids, her symptoms recurred with intermittent epigastric pain, facial pain, and sinusitis. She was then seen by rheumatology, and an autoimmune panel revealed positive anti-PR3 (27 RU/mL), negative anti-myeloperoxidase, and normal immunoglobulin G4 levels. Ultimately, a diagnosis of limited GPA, which spares the kidneys, was made, given the patient's clinical presentation and positive anti-PR3 antibody. Given that there was no lifethreatening organ involvement, she was started on methotrexate therapy and had significant improvement in her symptoms. The plan is to stay on methotrexate for at least 24 months and have regular follow-up to ensure clinical stability. To our knowledge, this is the first case report on acute pancreatitis as the initial presentation of limited GPA.

DISCUSSION
Gastrointestinal tract involvement is a rather rare entity in systemic vasculitides, especially GPA, and is often associated with poor prognosis. 4 In a case series of 62 patients with vasculitis, gastrointestinal involvement was identified in only 5%-11% of GPA cases, compared with 30%-56% in microscopic polyangiitis and 40%-60% in polyarteritis nodosa. 3 Pancreatic disease is even rarer; in fact, only 3 patients in that series had acute pancreatitis, and none of them had GPA. 3 This certainly suggests that pancreatic involvement is exceedingly rare in GPA and even rarer as the initial presentation of the disease. 5 Given this rare association, vasculitis is often overlooked in patients with idiopathic acute pancreatitis. 6 As such, the diagnosis is often delayed as patients develop other manifestations of the disease or even until they present with life-threatening end-organ damage. 7 This highlights the importance of having a high clinical suspicion for systemic vasculitis in cases of idiopathic pancreatitis and the important role of collaborative multidisciplinary involvement in multisystemic patient presentations. This allows for early recognition, timely treatment, and best possible outcomes for the patient.
It is interesting to note that our patient had an atypical presentation for GPA because there was no evidence of any respiratory or renal involvement clinically or radiologically. This    was most consistent with a diagnosis of limited GPA, which is uncommon but reported in previous case reports where there was pulmonary and/or renal sparing. 8 This makes our case unique firstly, given the diagnosis of limited GPA which is different from other GPA pancreatitis case reports where patients had other organ involvement simultaneously (Table 1). However, it is also possible that our patient was diagnosed and treated before disease progression to involve other organ systems. Second, our patient had always been relatively stable, with only brief hospital admissions for pancreatitis, and did not require any acute treatments for her vasculitis. Besides an empiric trial of short steroid course, she did not require any pulse methylprednisolone or induction immunosuppressive therapies (eg, cyclophosphamide or rituximab). This is in contrast to previous literature where gastrointestinal involvement predicted more severe disease, often with very poor outcomes despite aggressive treatment. 9,10 Nevertheless, it is important to continue close observation and have a low threshold for multiorgan screening while our patient is maintained on methotrexate therapy.
In summary, acute pancreatitis is a rare initial presentation of GPA vasculitis, and the diagnosis is often challenging in the absence of other organ involvement. Here, we illustrated a case of GPA presenting initially as acute pancreatitis, and it is quite atypical in its disease progression. As such, it is important to consider autoimmune diseases and systemic vasculitides in idiopathic pancreatitis after ruling out other common causes. A high clinical suspicion allows for early diagnosis and timely treatment with immunosuppressive therapy which achieves remission in 85%-90% of patients and increases survival. 11,12 This knowledge is important for clinicians to keep a broad differential and consider vasculitides in clinical practice for prompt diagnosis and best patient outcomes.